A multidisciplinary program of clinical and basic research designed to further elucidate the etiology, pathogenesis, ultrastructural abnormalities and protein manifestations of parkinsonism and allied basal ganglia disorders with the major objective of improving their diagnosis and treatment. Clinical studies will include a genetic analysis of monozygotic twins, measurement of drug and neurotransmitter metabolites in blood and CSF, assessment of present modes of therapy, trials of new therapeutic agents and physiological analyses of autonomic and visual dysfunction. Post-mortem brain tissue and surgical biopsy specimens will be subjected to histochemical, quantitative morphological, biochemical and microbiological investigations. The pathogenesis of experimental lesions of monoaminergic neuronal systems induced by viruses, chemical agents and endogenously formed cytoxic metabolites of dopamine will be studied in vitro, in animal models, in tissue cultures and organotypic cultures of the basal ganglia. An understanding of the modus operandi of therapeutic agents and of neurotransmitter metabolism will be sought in nigral and striatal lesioned animal models. The morphology and plasticity of dopamine and GABA receptors and the ultrastructure of brain actin and myosin-like protein will be further defined in relation to fundamental mechanisms of neurotransmission.